Water → HCID 57995653, compound

HRID 385364Notes

Reaction equation

HRID 385364 reaction equation
[CH2:1]([O:3][C:4](=[O:25])[CH2:5][C:6]1[CH:11]=[C:10]([O:12][CH2:13][C:14]([F:17])([F:16])[F:15])[C:9](I)=[C:8]([O:19][CH2:20][C:21]([F:24])([F:23])[F:22])[CH:7]=1)[CH3:2].[F:26][C:27]([F:38])([F:37])[C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1.[F-].[Cs+].O>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(C)=O>[CH2:1]([O:3][C:4](=[O:25])[CH2:5][C:6]1[CH:11]=[C:10]([O:12][CH2:13][C:14]([F:17])([F:16])[F:15])[C:9]([C:31]2[CH:32]=[CH:33][C:28]([C:27]([F:38])([F:37])[F:26])=[CH:29][CH:30]=2)=[C:8]([O:19][CH2:20][C:21]([F:24])([F:23])[F:22])[CH:7]=1)[CH3:2]

Participants

8

Reactant 4

HCID 962WaterHCID 25953Cesium fluorideHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 57995599HCID 57995599, compound

Product 1

HCID 57995653HCID 57995653, compoundYield 70%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of [4-iodo-3,5-bis-(2,2,2-trifluoro-ethoxy)-phenyl]-acetic acid ethyl ester (0.8 g, 1.65 mmol) in DME (anhydrous, 15 mL) under argon atmosphere were added 4-trifluoromethylphenylboronic acid (0.4 g, 2.10 mmol), CsF (0.6 g, 3.95 mmol), and Pd(PPh3)4 (0.3 g, 0.26 mmol). The reaction mixture was refluxed for 18 h (oil bath, 100° C.). A mixture of water and EtOAc (15 mL/15 mL) was added and the layers were separated. The organic phase was dried over MgSO4 and evaporated to give a crude yellow oil, which was purified by silica gel gradient column chromatography by use of Heptane-EtOAc (20:1-9:1) to give [2,6-bis-(2,2,2-trifluoro-ethoxy)-4′-trifluoromethyl-biphenyl-4-yl]-acetic acid ethyl ester (0.54 g, 70%) as a yellowish oil. 1H NMR (300 MHz, CDCl3/TMS): δ 7.64 (d, J=8.2 Hz, 2H), 7.46 (d, J=8.0 Hz, 2H), 6.68 (s, 2H), 4.28-4.16 (6H), 3.63 (s, 2H), 1.29 (t, J=7.2 Hz, 3H). 13C NMR (75 MHz, CDCl3/TMS): δ 170.6, 155.3, 136.1, 135.5, 131.0, 129.4, 129.0, 124.4 (q, 3JCF=3.9 Hz), 124.2, 122.9, 119.0, 109.2 (two signals), 66.5 (q, 2JCF=35.5 Hz), 61.3, 41.5, 14.2.

Workup

  1. additionwas added
  2. customthe layers were separated
  3. dry with materialThe organic phase was dried over MgSO4
  4. customevaporated
  5. customto give a crude yellow oil, which
  6. customwas purified by silica gel gradient column chromatography by use of Heptane-EtOAc (20:1-9:1)

Sources & evidence

ORD record
ord-10969cb14555430386ebb7188d8b1f58
Source dataset
uspto-grants-2013_02
Patent number
US08367863B2

Reaction notes

Loading…